I understand that enkephalins are similar in activity and function to endorphins. Enkephalins  lead to depressed breathing, act as analgesics, and do various other actions you would expect from an opioid. This is because enkephalins are opioids.  Enkephalinase is an enzyme that lowers the concentration of enkephalins by degrading them. If one prevents the degradation of enkephalins, using an enkephalinase inhibitor, such as lactucopicrin, or possibly what is in Salvia Nemorosa,  the enkephalins will increase leading to something similar to a runners high but without the need for running. 
   However, they will not continue to increase allowing you to get higher and higher. There are some limiting factors such as how much your body can, how effectively the enkephalinase enzymes were inhibited, and also how your body will compensate by adjusting  to the levels of enkephalins present.
   Does any one know of other enkephalinase inhibitors, possibly synthetic ones,  or have any ideas how to make their potential high more even higher? Perhaps whatever enzymes might degrade the inhibitors could be inhibited by something else. I know great fruit has a lot of chemicals that inhibit various enzymes used in metabolism.
What do you guys think of this idea…. Either before or after taking an enkephalinase inhibitor  eat very spicy foods - this would increase the amount of enkephalins in the body, leading to much more of a high then had you chosen to only take the hot food, or only the inhibitor.
Also do you think enkaphalinase inhibitors has potential for addiction? I am sure they have slight potential for a psychological dependence, but does it have any physiological risks for addiction? Perhaps since more enzymes are inhibited, the body might produce more - making it so when the drug is not in your body the enkaphalins would be degraded to quick. This could possibly lead to a slight feeling of opiate withdrawal.


here are some interesting links:

http://en.wikipedia.org/wiki/NPEPPS
http://en.wikipedia.org/wiki/Lactucopicrin
http://en.wikipedia.org/wiki/Lactucarium
http://en.wikipedia.org/wiki/Enkephalin

"D-phenylalanine, bacitracin and puromycin produce long-lasting, naloxone-reversible analgesia in mice. Analgesic potency parallels potency of these compounds as inhibitors of met-enkephalin degradation by mouse brain enzymes. D-phenylalanine potentiates acupuncture analgesia in mice and humans and has been used to ameliorate a variety of human chronic pain conditions." - http://www.ncbi.nlm.nih.gov/pubmed/2934746



"Pharmacological properties of acetorphan, a parenterally active "enkephalinase" inhibitor

JM Lecomte, J Costentin, A Vlaiculescu, P Chaillet, H Marcais-Collado, C Llorens-Cortes, M Leboyer and JC Schwartz

Acetorphan, i.e. N-[(R,S)-3-acetylmercapto-2-benzylpropanoyl]-glycine, benzyl ester, is a lipophilic derivative of Thiorphan, a potent inhibitor of "enkephalinase" (EC 3.4.24.11). On purified enkephalinase its inhibitory potency was approximately 1000 fold less than that of Thiorphan but became close to the latter (nanomolar) when it was incubated previously with cerebral membranes. After parenteral administration to mice and rats (1-10 mg/kg) extensive inhibition of cerebral enkephalinase was shown by the depressed enzyme activity in brain membranes from treated animals and the long-lasting potentiation of analgesia elicited by (D-Ala2,Met5)enkephalin (i.c.v.). This suggests that acetorphan easily enters the brain where the active Thiorphan is released. Parenteral acetorphan elicited a series of naloxone-reversible, opioid-like effects, most of which were described previously with intracerebral Thiorphan or other enkephalinase inhibitors. Antinociceptive effects were found in some tests (hot plate jump and phenylbenzoquinone-induced writhing) but not in others (hot plate licking and tail withdrawal). "Antidepressant" effect was found in the "mouse despair" test and antidiarrhoeal effect in the rat castor oil test. Acetorphan also elicited significant increases and decreases in turnover indexes of serotonin and noradrenaline, respectively, in mouse cerebral cortex. In mice chronically treated with acetorphan, the antinociceptive activity of the compound was not modified markedly and no overt withdrawal symptom could be observed after either treatment interruption or administration of naloxone. " -- http://jpet.aspetjournals.org/cgi/content/abstract/237/3/937

I was also talking with hypnos about this (payback for the old morphine in the breast milk trick);

Pregnancy
A placental tissue of foetal origin — i.e. the syncytiotrophoblast — excretes beta-endorphins into the maternal blood system from the 3rd month of pregnancy. A recent study [25] proposes an adaptive background for this phenomenon. The authors argue that foetuses make their mothers endorphin-dependent then manipulate them to increase nutrient allocation to the placenta. Their hypothesis predicts that: (1) anatomic position of endorphin production should mirror its presumed role in foetal-maternal conflict; (2) endorphin levels should co-vary positively with nutrient carrying capacity of maternal blood system; (3) postpartum psychological symptoms (such as postpartum blues, depression and psychosis) in humans are side-effects of this mechanism that can be interpreted as endorphin-deprivation symptoms; (4) shortly after parturition, placentophagy could play an adaptive role in decreasing the negative side-effects of foetal manipulation; (5) later, breast-feeding induced endorphin excretion of the maternal pituitary saves mother from further deprivation symptoms. These predictions appear to be supported by empirical data.[25]

http://en.wikipedia.org/wiki/Endorphin

Deal in the womb: Fetal opiates, parent-offspring conflict, and the future of midwifery
Pe´ter Apari a, Lajos Ro´zsa
Medical Hypotheses (2006) 67, 1189–1194
http://www.zoologia.hu/list/apari_rozsa.pdf

On wikipedia about RB-101:

"A significant advantage of inhibiting the breakdown of endogenous opioid peptides rather than stimulating opioid receptors with exogenous drugs is that the levels of opioid peptides are only increased slightly from natural levels, thus avoiding overstimulation and downregulation of the opioid receptors. This means that even when RB-101 is used in high doses for extended periods of time, there is no development of dependence on the drug or tolerance to its analgesic effects.[12][13]  Consequently even though RB-101 is able to produce potent analgesic effects via the opioid system, it is unlikely to be addictive.[14]"

So you can get an opiate high without addiction tolerance or respiratory depression. Sounds great to me.

"Pharmacological properties of acetorphan, a parenterally active "enkephalinase" inhibitor

JM Lecomte, J Costentin, A Vlaiculescu, P Chaillet, H Marcais-Collado, C Llorens-Cortes, M Leboyer and JC Schwartz

Acetorphan, i.e. N-[(R,S)-3-acetylmercapto-2-benzylpropanoyl]-glycine, benzyl ester, is a lipophilic derivative of Thiorphan, a potent inhibitor of "enkephalinase" (EC 3.4.24.11). On purified enkephalinase its inhibitory potency was approximately 1000 fold less than that of Thiorphan but became close to the latter (nanomolar) when it was incubated previously with cerebral membranes. After parenteral administration to mice and rats (1-10 mg/kg) extensive inhibition of cerebral enkephalinase was shown by the depressed enzyme activity in brain membranes from treated animals and the long-lasting potentiation of analgesia elicited by (D-Ala2,Met5)enkephalin (i.c.v.). This suggests that acetorphan easily enters the brain where the active Thiorphan is released. Parenteral acetorphan elicited a series of naloxone-reversible, opioid-like effects, most of which were described previously with intracerebral Thiorphan or other enkephalinase inhibitors. Antinociceptive effects were found in some tests (hot plate jump and phenylbenzoquinone-induced writhing) but not in others (hot plate licking and tail withdrawal). "Antidepressant" effect was found in the "mouse despair" test and antidiarrhoeal effect in the rat castor oil test. Acetorphan also elicited significant increases and decreases in turnover indexes of serotonin and noradrenaline, respectively, in mouse cerebral cortex. In mice chronically treated with acetorphan, the antinociceptive activity of the compound was not modified markedly and no overt withdrawal symptom could be observed after either treatment interruption or administration of naloxone. " -- http://jpet.aspetjournals.org/cgi/content/abstract/237/3/937

Here's the full article for you.

Bet they would be good for coming off opioids.

I might get a some of the  Nigella essential oil actually, since I am stuck taking DHC for chronic pain, and whilst actually quitting isn't an option, well, not if I want to be able to walk much distance, being forced to take it all the time or feel like shit is not my idea of fun.

Wish I could find some naltrexone though, the ULDN protocol looks like the shit as far as tolerance goes.

I know some pain patients find better relief from low doses (at least compared to what some use) of Methadone. I don't know your specfic situation but it could be something for you to look into.

welcome to the chronic pain club at least you can get medicated for your pain here it's a different story.
the dea is so hot on doctors right now you have to be dying before you get proper meds.
i'm in the same boat now it keeps me bedridden and living under constant supervision there's no way i can do anything about it my pain was so severe at one point my blood pressure was 170 over 110 and pulse about 120 for months, and this is after a cerbrovascular accident and renal failure in effect putting me in  jeopardy of another stroke and or kidney failure.
they had me on 3 blood presure meds but they did'nt work because the underlying cause (sever pain) was'nt addressed.

Nice link. Found it very interesting, and also found out about this drug that seems to be available to everyone but the US.
http://en.wikipedia.org/wiki/Racecadotril

It is apparently metabolized into an enkaphalinase inhibitor - however, it doesn't seem like it crosses the BBB. However, I bet it could be modified to do so farily easily.
Or at least its metabolite could be, which is Thiorphan, an organic acid -- likely forming an alkylamide with it could aid in it crossing the blood brain barrier?